HIGH THYROPEROXIDASE ANTIBODY TITERS MAY PREDICT RESPONSE TO ANTITHYROID DRUG TREATMENT IN GRAVES DISEASE: A PRELIMINARY STUDY.

Background and aim: Antithyroid drugs are first treatment for Graves hyperthyroidism worldwide. Although remission can be achieved in approximately 40-50% of patients in 12-18 months with antithyroid drugs, this period can be extended up to 24 months. We aimed to evaluate the effect of individual clinical/biochemical variables and GREAT score in predicting response to antithyroid drug in Graves disease. Material and methods: This is a retrospective single-center study including 99 patients with the first episode of Graves disease treated for at least 18 months. The patients were classified into two groups as those who responded to antithyroid medication at 18-24 months (group 1) and those who did not respond at 24 months and continued with low-dose antithyroid medication (group 2). Results: Medical treatment response was obtained in 38 (38.3%) of the patients at 18 months, and in 19 (19.1%) patients at 24 months. Long-term medical treatment (>24 months) was given to the remaining 43 patients due to the lack of response to medical treatment. Thyroid volume and free T4 levels were higher in those followed up with long-term antithyroid drugs, and orbitopathy was more common in this group. Median anti TPO value was significantly higher in group 1 when compared to group 2 (593 U/l and 191.6 U/l respectively). More patients were classified as GREAT class 3 in group 2 when compared to group 1 (46.5% and 12,5% respectively). We analyzed the Thyroperoxidase Antibody(anti TPO) titers, which we divided into three levels, according to groups 1 and 2. Post-hoc Chi-Square analysis revealed that falling into the highest anti TPO category was significantly associated with response to medical therapy in 24 months (p <0.05). Conclusion: According to our study, GREAT score and anti TPO Ab titers at presentation may help predict response to ATD in Graves disease.

Metabolic role of hepassocin in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a female endocrinopathy characterized by hyperandrogenemia, insulin resistance, glucose intolerance, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), and obesity. Hepassocin (HPS) is a hepatokine involved in energy and lipid metabolism. We aimed to investigate the role of HPS in metabolic dysfunction and its relationship with fatty liver in patients with PCOS. PATIENTS AND METHODS: A total of 45 newly diagnosed PCOS patients and 42 healthy women of similar age were included in the study. Routine anthropometric, biochemical, and hormonal information were recorded. Serum HPS and high-sensitivity C-reactive protein (hsCRP) were measured, and NAFLD fibrosis score (NFS) and Fibrosis-4 (FIB-4) were calculated and correlated. RESULTS: HPS and hsCRP values of the PCOS group were found to be significantly higher than controls (p=0.005, p<0.001, respectively). A positive correlation was found between both HPS and hsCRP and luteinizing hormone (LH) (p<0.001). No correlation was observed between HPS and NFS and FIB-4, however, only a weak negative correlation was observed between hsCRP and FIB-4. A negative correlation was found between HPS and BMI, waist circumference, fat ratio, and HbA1c (p<0.05). In multivariate regression analysis for HPS, R-squared is 0.898, and hsCRP, neck circumference, fat amount, and LH are significant factors. CONCLUSIONS: NAFLD is an important dysmetabolic component of PCOS. Serum HPS is elevated in PCOS patients. We found a positive correlation between hsCRP and LH and a negative correlation between obesity indices, although we did not find an association between NFS and FIB-4, and HPS. In the future, large-scale molecular studies of HPS may be beneficial.

Evaluation of the effects of empagliflozin on acute lung injury in rat intestinal ischemia-reperfusion model.

BACKGROUND: Empagliflozin is a selective sodium-glucose co-transporter (SGLT2) inhibitor that is approved for the treatment of type 2 diabetes. The beneficial effects of empagliflozin on other organ systems including the heart and kidneys have been proven. The aim of this study is to evaluate the role of empagliflozin on acute lung injury induced by intestinal ischemia-reperfusion (I/R). MATERIALS AND METHODS: A total of 27 male Wistar albino rats were divided into three groups: sham, I/R, and I/R + empagliflozin; each group containing nine animals. Sham group rats underwent laparotomy without I/R injury. Rats in the I/R group underwent laparotomy, 1 h of after ischemia-reperfusion injury (superior mesenteric artery ligation was followed by 2 h of reperfusion). Rats in I/R were given empagliflozin (30 mg/kg) by gastric gavage for 7 days before the ischemia-reperfusion injury. All animals were killed at the end of reperfusion and lung tissue samples were obtained for immunohistochemical staining and histopathological investigation in all groups. RESULTS: Serum glucose, AST, ALT, creatinine, native thiol, total thiol, and disulfide levels and disulfide-native thiol, disulfide-total thiol, and native thiol-total thiol ratios as well as the IMA levels were analyzed and compared among the groups. While intestinal I/R significantly increases serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels; did not cause any change in homeostasis parameters and IMA level. Empagliflozin treatment had no significant effect on biochemical parameters. Empagliflozin treatment induced a significant decrease in positive immunostaining for IL-1, IL-6, TNF-alpha, caspase 3, caspase 8, and caspase 9 compared to the I/R group in lung tissue samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. Empagliflozin treatment significantly attenuated the severity of intestinal I/R injury. CONCLUSIONS: It was concluded that empagliflozin treatment may have beneficial effects in acute lung injury, and, therefore, has the potential for clinical use.

Sonographic evaluation of subclinical entheseal involvement in patients with hypoparathyroidism: a case control study.

PURPOSE: Hypoparathyroidism is a disease characterized by low serum calcium, increased serum phosphorus and low PTH levels. Although patients are treated with active vitamin D and calcium, a proper serum calcium phosphorus balance cannot always be achieved. Ectopic calcifications that develop in organs during treatment are the most common complications. To date, there is not any published study on enthesopathy in patients with hypoparathyroidism. The aim of this study was to evaluate subclinical enthesopathy in patients with hypoparathyroidism with ultrasound and to compare the results with those of the control group. METHODS: The study included patients aged 18-65 years with postoperative hypoparathyroidism and hypothyroidism (group hypoP + hypoT), patients with postoperative hypothyroidism (group hypoT), and healthy age and sex-matched volunteers (group C). Ultrasonographic findings of enthesopathy in both extremities were documented according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). RESULTS: GUESS scores in group hypoP + hypoT, were significantly higher when compared to the other groups. There was a statistically significant correlation between the total GUESS scores and total enthesophyte scores and the duration of hypoparathyroidism (p < 0.05, r = 0.43) (p < 0.05, r = 0.39) respectively. In the correlation analysis of all groups, a significant negative correlation was found between serum Ca and PTH levels and the total GUESS scores (p < 0.01, r = - 0.37; p < 0.01, r = - 0.54, respectively). CONCLUSION: This study showed that GUESS scores were significantly higher in patients with hypoparathyroidism compared to those with hypothyroidism and control subjects. GUESS scores were positively correlated with disease duration. Patients with hypoparathyroidism need to be evaluated for subclinical enthesopathy during follow-up.

Factors that affect the Glycemic Control Achieved by Switching to Insulin Degludec/ Aspart in Insulin-Treated Patients with Type 1 and Type 2 Diabetes in a Real-World Setting: a Non-interventional, Retrospective Cohort Study.

BACKGROUND: Insulin degludec/aspart (IDegAsp) is a co-formulation with IDeg and IAsp. Different insulin regimens may be switched to IDegAsp. In this study, we aimed to find out the effect of switch to IDegAsp on glycemic control and whether the basal characteristics and treatment modalities of the patients affect the change in glycemic control brought by switch to IDegAsp. METHODS: We retrospectively analyzed the records of 78 patients whose insulin therapies (basal+bolus, premixed analogues or basal only) were switched on a 1:1 unit basis to IDegAsp±bolus insulin. Oral antidiabetic agents (OADs) given were recorded. At the end of 12th and 24th week, total insulin doses of patients and HbA1c were compared to the baseline. RESULTS: There was a statistically significant decrease at HbA1c at 12 weeks (1.4%; p<0.001). There was not a significant difference in HbA1c between the OAD added group and the group with no new OADs(p=0.1). Basal insulin dose was not statistically different from baseline, whereas bolus insulin dose was significantly lower (p=0.007). At the end of 24 weeks the decrease in HbA1c level from baseline was preserved. CONCLUSION: Regardless of the baseline insulin regimen, diabetes type and oral antidiabetic drugs given, HbA1c is significantly lowered after switching to IDegAsp.

ECTOPIC LINGUAL THYROID PRESENTING WITH MASSIVE HEMATEMESIS.

Ectopic lingual thyroid is a rare developmental abnormality caused by aberrant embryogenesis during thyroid migration. Even though, most patients are asymptomatic, uncommonly the mass can be enlarged and cause dysphagia, dyspnea, upper airway obstruction, dysphonia, hypothyroidism. We report a very rare case of ectopic lingual thyroid presenting with massive hematemesis.

The evaluation of preoperative and postoperative fetuin-A levels in patients with primary hyperparathyroidism.

OBJECTIVES: Our objective was to evaluate preoperative and postoperative serum fetuin-A levels in female patients with primary hyperparathyroidism (PHPT) and search for the relationship with parathyroid hormone (PTH) and vitamin D (25OHD). Although a role for fetuin-A is suggested in regulating bone mineralization, its function has not been completely defined. MATERIALS AND METHODS: In this cross-sectional study, 43 female patients with PHPT and 30 healthy women were recruited as the control group. We evaluated 73 women because we had only women patients with PHPT. Of the 43 patients, 10 symptomatic and 23 asymptomatic patients were surgically treated, whereas 10 patients were not operated. In all 43 patients, 25OHD, PTH, fetuin-A levels, and bone mineral densitometry were evaluated. The biochemical parameters of 33 operated patients were reevaluated at the postoperative sixth week. RESULTS: Fetuin-A levels of the patients with PHPT were significantly higher than that in the controls (56.6 ± 13.8 vs. 42.6 ± 20.7 ng/mL; P = 0.010). Fetuin-A levels of the operated patients were higher than nonoperated group. Furthermore, serum fetuin-A levels of the nonoperated patients were not different from those of controls. After parathyroidectomy, fetuin-A (41.5 ± 25.2 vs. 56.4 ± 13.7 ng/mL; P = 0.003), PTH [80.0 (51.5-137.5) vs. 211.0 (151.5-278.5) pg/mL; P < 0.001], and calcium (9.2 ± 0.7 vs. 10.7 ± 0.8 mg/dL; P < 0.001) values were found to be decreased significantly. CONCLUSION: In this study, fetuin-A levels of patients with PHPT were higher than those of the controls and significantly decreased after parathyroidectomy compared with the preoperative levels. Fetuin-A levels could be a beneficial marker to determine the changes in bone metabolism of the patients with PHPT and to detect the patients suitable for surgery.

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis.

PURPOSE: Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). METHODS: Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. RESULTS: Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = -0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. CONCLUSION: The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic.

Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from Pituitary Study Group database.

Hypopituitarism in adult life is commonly acquired and the main causes are known as pituitary tumors and/or their treatments. Since there are new insights into the etiology of hypopituitarism and presence of differences in various populations, more studies regarding causes of hypopituitarism are needed to be done in different ethnic groups with sufficient number of patients. Therefore, we performed a multi-center database study in Turkish population investigating the etiology of hypopituitarism in 773 patients in tertiary care institutions. The study was designed and coordinated by the Pituitary Study Group of SEMT (The Society of Endocrinology and Metabolism of Turkey). Nineteen tertiary reference centers (14 university hospitals and 5 training hospitals) from the different regions of Turkey participated in the study. It is a cross-sectional database study, and the data were recorded for 18 months. We mainly classified the causes of hypopituitarism as pituitary tumors (due to direct effects of the pituitary tumors and/or their treatments), extra-pituitary tumors and non-tumoral causes. Mean age of 773 patients (49.8 % male, 50.2 % female) was 43.9 ± 16.1 years (range 16-84 years). The most common etiology of pituitary dysfunction was due to non-tumoral causes (49.2 %) among all patients. However, when we analyze the causes according to gender, the most common etiology in males was pituitary tumors, but the most common etiology in females was non-tumoral causes. According to the subgroup analysis of the causes of hypopituitarism in all patients, the most common four causes of hypopituitarism which have frequencies over 10 % were as follows: non-secretory pituitary adenomas, Sheehan's syndrome, lactotroph adenomas and idiopathic. With regard to the type of hormonal deficiencies; FSH/LH deficiency was the most common hormonal deficit (84.9 % of the patients). In 33.8 % of the patients, 4 anterior pituitary hormone deficiencies (FSH/LH, ACTH, TSH, and GH) were present. Among all patients, the most frequent cause of hypopituitarism was non-secretory pituitary adenomas. However, in female patients, present study clearly demonstrates that Sheehan's syndrome is still one of the most important causes of hypopituitarism in Turkish population. Further, population-based prospective studies need to be done to understand the prevalence and incidence of the causes of hypopituitarism in different countries.

Helicobacter pylori prevalence in diabetic patients and its relationship with dyspepsia and autonomic neuropathy.

AIMS: We evaluated the prevalence of Helicobacter pylori (HP) in Type 2 diabetic patients and its relationship with dyspeptic symptoms and complications of diabetes. MATERIALS AND METHODS: Seventy-eight Type 2 diabetic patients (54 females, 24 males, mean age: 51.9 +/- 10.6 yr) and 71 non-diabetic control subjects were involved in the study. Patients were questioned for dyspeptic symptoms. Cardiovascular autonomic neuropathy, nephropathy and retinopathy were investigated in diabetic patients. Upper gastrointestinal tract endoscopy was performed for all patients and gastric biopsies were obtained and searched for HP. RESULTS: Helicobacter pylori prevalence was significantly higher in diabetic patients than in control subjects (75.6 vs 46%, p < 0.05). No differences were found between women and men with regard to HP infection status in diabetic patients. There was no relation between HP and diabetic complications, nephropathy and retinopathy. Helicobacter pylori prevalence was significantly higher in diabetic patients with cardiovascular autonomic neuropathy than in diabetic patients without cardiovascular autonomic neuropathy (90.6 vs 44.0%, p < 0.02). Forty-seven subjects with diabetes had symptoms of dyspepsia (60.3%) and the prevalence of HP was higher in these patients (p < 0.002). CONCLUSION: There is a high prevalence of HP infection in diabetic patients and it is correlated with dyspeptic symptoms. Diabetic subjects complicated with cardiovascular autonomic neuropathy and dyspepsia are at high risk of HP infection and should be carefully investigated and considered for eradication therapy.

Metformin versus flutamide in the treatment of metabolic consequences of non-obese young women with polycystic ovary syndrome: a randomized prospective study.

In addition to the reproductive consequences, polycystic ovary syndrome (PCOS) is characterized by a metabolic disorder in which hyperinsulinemia and insulin resistance are central features. The effects and possible benefits from insulin-sensitizing drugs are not well known, especially in non-obese women with PCOS. This study was designed to evaluate the effects of metformin and flutamide on metabolic parameters and insulin resistance in non-obese women with PCOS. Thirty non-obese women newly diagnosed with PCOS and 15 age- and weight-matched healthy volunteers as controls were included in the study. Patients were assigned randomly to receive flutamide 250 mg daily or metformin 850 mg three times daily. Glucose, insulin, insulin resistance, androgen levels and glucose and insulin responses to an oral glucose tolerance tests (OGTT) were assessed before and after a 4-week therapy period. A positive correlation was found between body mass index and insulin level in patients with PCOS and controls. Follicle stimulating hormone, luteinizing hormone, free testosterone and dehydroepiandrosterone sulfate levels decreased significantly, but insulin resistance levels were not changed after flutamide therapy. Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy. In conclusion, metformin treatment improved insulin sensitivity and decreased androgen levels, and flutamide decreased androgen levels but failed to improve insulin sensitivity in the non-obese women with PCOS.

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism.

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.